Well it depends...
If you already SAV for Domino, then enabling the Notes plugin is redundant and therefore not needed.
Same with Outlook, it you already have AV for Exchange then enabling this plugin is not needed.
The benefits are if you DON'T have some other form scanning then you should enabled these to be further protected. Not enabling them could you leave you open to viruses via email.
WIndows exclusions will needed for various programs you have on your computers. These will need to be decided by you.
Setting exclusions can lead to improved performance and unnecessary scanning of certain directories.
Obviously, not setting exclusions if you need them can cause you some performance headaches.